Ex vivoDetermination of an Estradiol Analogue-Induced Changes on Platelet Morphology and Angiogenic Biomarkers

Abstract

Angiogenesis is a closely controlled biological process that takes place during fetal development of blood vessels and wound healing, and includes the development of new blood vessels from preexisting blood vessels. Tumor angiogenesis is a means by which tumors obtain oxygen, nutrition and promote tumor growth. Angiogenesis-regulating proteins are therefore ideal biomarkers in the study of tumor pathophysiology. In our laboratory, a new in silico-designed analogue of 2-methoxyestradiol has been synthesized with angiogenic properties, namely 2-ethyl-3-O-sulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16). The ex vivo influence of ESE-16 on angiogenesis and morphology in platelets of healthy participants was investigated. Scanning electron microscopy revealed no morphological changes in ESE-16-treated platelets. The possible antiangiogenic effect of ESE-16-exposed platelets was determined by means of flow cytometry measurement of angiogenic protein levels, which were significantly increased after platelets were added to tumorigenic breast epithelial cells. This indicates that binding of platelets to cancer cells causes differential release of platelet constituents. Vascular endothelial growth factor levels were decreased in platelets, whereas platelet-derived growth factor and matrix metallopeptidase-9 levels were not significantly affected in platelets. In light of the above-mentioned data, further investigation of ESE-16's influence on morphology and angiogenic markers in platelets of cancer patients is warranted.

Secretomics reveals hormone-therapy of breast cancer may induce survival by facilitating hypercoagulation and immunomodulation in vitro

“…In the present study downregulation of secreted von Willebrand factor and anti-thrombin was postulated to be associated with a positive feedback loop that illustrated platelet activation, particularly by MCF7 cells under both hormone-therapies. Morphologically, platelets showed clear extension of pseudopodia and hyalomere spread, morphological changes indicative of early degranulation 45 . We also illustrated through proteomic analysis, pathways that were enriched following both Tamoxifen and Anastrozole treatment of MCF7 cells, included those involved in platelet degranulation and initiation of the clotting cascade.…”